We have developed an electrospray ionization mass spectrometer system for the purpose of determining molecular weights of large molecules with accuracy and precision greater than is possible by other techniques. The approach we took was to use a 500 um ID x 30 cm long heated metal capillary for transport and desolvation of multiply charged droplets formed in the atmospheric pressure electrospray. The capillary output was coupled into a 2 stage pressure reduction system that delivered desolvated multiply charged ions to the quadrupole mass analyzer. Preliminary results with this ionization source include spectra of insulin (mw approx. 5700 Da), cytochrome c (mw approx. 12600) and carbonic anhydrase (mw approx. 29,000). Molecular weight determinations from deconvoluting the envelope of multiply charged ion species have been quite satisfactory to date. We have observed cytochrome c to have an envelope of peaks containing between 10 and 17 charges at m/z values ranging from 728 to 1376.5 Da. From these observations, we have calculated the molecular weight to be 12,362.2 +/ 8.8 Da compared to the accepted value of 12,360.9. Our determinations represent a relative standard deviation of 0.1% and a relative accuracy of 100 ppm. Sensitivity of this approach has been investigated with a small molecule, 1,25-(OH)2 vitamin D. We found that it was possible to obtain a response with signal-to-noise of >10:1 for a sample flowing at 5 fmole/min. This represents an improvement of about 400:1 compared to thermospray for this molecule. Immediate application of these results await the development of an appropriate LC/MS interface for electrospray.